Synaptic Conversion of Chloride-Dependent Synapses in Spinal Nociceptive Circuits: Roles in Neuropathic Pain

Figure 6

Psychophysiologic pain can potentially arise when descending GABAergic neurons from supraspinal sites drive spinal nociceptive circuits that have been altered by synaptic conversion. The anterior cingulate cortex (ACC) becomes activated during strong emotional states (e.g., anger or fear), as well as during psychological conflict [26]. The ACC also regulates the experience of pain, as well as the anticipation of pain. The ACC drives the periaqueductal grey (PAG) region of the midbrain [27], which in turn drives the nucleus raphe magnus (NRM), as well as the rostral ventrolateral medulla (RVM). GABAergic fibers that descend from the NRM and RVM innervate lamina I projection neurons in the dorsal horn of the spinal cord. When the projection neuron has abnormally high intracellular chloride (i.e., a chloride-opathy), the descending GABAergic drive becomes pro-nociceptive [24]. Normally, this drive is antinociceptive. Thus, a major pain coping mechanism, originating at supraspinal levels, is compromised by neuroinflammation and chloride-opathies at the spinal level.